WHY LEAKY GUTS LEAD TO MS?

WHY LEAKY GUTS LEAD TO MS?

READERS SUMMARY:
1. What determines our ultimate health fate?
2. What exactly is epigenetics?
3. How does an autoimmune disease begin?
4. Is multiple sclerosis tied to gut inflammation?
5. What is an inflammasome and why is hypomethylation so critical?

My first post on epigenetics seems to have stimulated a lot of talk based upon the emails I received. I think we need to dig a bit deeper into this area because it is now clear scientifically that epigenetics really determines our ultimate health outcomes. In fact, it is the easiest way to alter our genomes by modifying our dietary choices. To begin let’s simply define what epigenetics is in 2011. Epigenetics is any mechanism that affects genes without chaining the nucleotide sequence of the DNA. The two major ways epigenetic modification occurs via our diet is via methylation of our DNA or of acetylation of our histone proteins. The amount of methyl and acetyl groups come from our diets. For example, when we have low methylation in our diet, our DNA becomes hypomethylated. Lower levels of methylation correlates with development of higher rates of cancer and with autoimmune conditions. Obviously, none of us wants to get cancer or autoimmune disease so I think we all need to pay attention about how epigenetics can help keep us free of disease.

Cellular functioning determines health and sickness. This is the core of levee one. Many cellular functions also determine how we age. As soon as we are born aging commences. No one really perceives aging that way but they need to because the science of epigenetics is the engine driving that biologic fact. Most aging pathways intersect with many others simultaneously. Their collective summation over time is called the process of aging. All act in an interdependent fashion and epigenetic modification of our genome is one of those powerful forces that shape the fate of our cells. Remember that groups of cells function in unison to make our organs. Our organs form the basis of our physiology. The degree of exposure of an organ to a specific environmental factor can also determine its ability to induce specific alteration within that organ.

In the Paleo community we often hear about the effects of grains that cause autoimmune conditions like celiac disease and Hashimoto’s disease. We rarely hear how this really occurs. The answer is epigenetic modifications of our genome by the grains and how they interact with our gut’s immune system. That interaction occurs because of the constant assault of our immune system causes hypomethylation of our immune cells in the gut. This process leads to the formation of something called the “inflammasomes”. Inflammasomes are triggered by inflammation. This chronic inflammation triggers activation of specific danger associated diseases called (DAMP’s). Things you may know about that trigger DAMP’s are asbestos, silica, alum, BPA, and grains. These are examples of exogenous stressors. Some examples of endogenous stressors of the “inflammasome” are ATP, uric acid, Mitochondrial dysfunction, obesity, PUFA’s, ceramics, ROS and hyperglycemia. The inflammasome triggers an inflammatory cascade that eventually secretes cytokines IL-1Beta and IL-18. These cytokines eventually lead to the production of IL-6 and TNF alpha that we learned about in our leptin series. IL-6 and TNF alpha activate the 911 system (NF kappa beta) in our cells that signal major cellular suicide or recycling pathways within the cell. (apoptosis or autophagy). It also appears that obesity can produce unchecked activation of the inflammasome to provoke inflammation and cause autoimmune destruction of certain organs. This mechanism is now known to cause autoimmune diseases like type two diabetes, celiac, atherosclerosis, MS, and type one diabetes.

Today I want to talk about one autoimmune disease that I have gotten many questions about. That disease is multiple sclerosis (MS). In the past decade we have learned about new pattern recognition molecules called NOD like receptors (NLR). NLR’s recognize both pathogens and DAMP’s so they are important sensors of cellular stress that arises from bacteria or from cellular instability as it occurs. Clinical studies have identified an important role of inflammasome derived cytokines in MS pathogenesis. IL- 1 beta levels are correlated with the severity of MS disease a patient could face if they had MS. People with a high ratio of Il-1 beta compared to the IL-1R antagonists are epigenetically predisposed to developing MS. (Huang et al., 2004: Ming et al.,2002.) The correlation of IL 1 cytokines to neurodegenerative disorders is strengthened by the experimental autoimmune encephalomyelitis mouse model of MS disease as well. IL1 produces neuroinflammation by promoting the differentiation and production of IL-17 producing T cells that causes cell death of CNS myelin that characterizes MS plaques. Myelin is the covering of nerve cells. Think of it like the plastic covering on an electrical wire. When the plastic is pulled off the wire is exposed and subject to a “short circuit” and it wont work well.
Research is beginning to show that chronic inflammation from our gut, coupled with low vitamin D levels, and poor VDR receptor function allow for the activation of auto-reactive T cells that destroy cells that make the covering (myelin) of nerve cells. MS is a debilitating neuroinflammatory disease that occurs when auto-reactive T cells gain entry into the CNS and destroy myelin producing oligodendrocytes. It appears the T cells can enter the CNS via a leaky blood brain barrier that comes from a leaky gut or chronic inflammation of any sort. An early finding in MS patients but in all autoimmune disease in evolution is the constant finding of low levels of DHEA. Interestingly, when DHEA is replaced it has been shown to help limit the severity of disease progression. In some cases, the disease can be “pushed” to remission after it has been diagnosed when DHEA levels are treated. The DHEA level is felt to be down regulated because of the constant stress on the adrenal to make cortisol due to the non stop nature of the inflammatory cascade in autoimmune diseases. We call this low DHEA finding pregnenolone steal syndrome. DHEA is known to be a potent inhibitor of IL-6 and TNF alpha too! I am constantly amazed that this hormone is not assayed in all cases of autoimmunity and replaced.

WRAPPING IT UP: Today the treatment of MS revolves around Interferon beta use (IFN-B). IFN-B works because it decreases the production of IL-1beta from the inflammasomes. It does this by limiting the activation of the inflammasome to begin with. Real advancements in treatment of MS will occur when we figure out precisely what interactions are with the food choices and how they interact in our gut with the bacteria and immune system that lead to the generation of these auto-reactive T cells.

For now, we understand that the likely causation of MS is tied to chronic inflammation from our diet that initiates the irritation of the gut. This gut irritation induces epigenetic changes in our immune cells in the gut associated lymphoid tissue (GALT) to cause DNA hypomethylation sequences that eventually lead to the formation of inflammasomes. These inflammasomes produce inflammatory cytokines that further modify our immune cells to become auto-reactive cells to our own myelin coating of our nerves cells to cause short circuits all over our brain and spinal cord in multiple sclerosis patients. It now appears that any disease that causes chronic inflammation can induce autoimmune reactive cells to form. This is why we see many associations of inflammatory diseases to autoimmune diseases. The factor tying these diseases together is epigenetic modification of certain parts and cells of our immune system so that they can no longer protect our organs and instead begin to slowly destroy them overtime and result in disease propagation.

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Dr Kruse, I have read a little about methylation before, but I don't recall if there is a way to test ones own methylating abilities. Could this be useful for paleo-type eaters who consume large amounts of methionine?

Interesting! For some reason I found this blog post much easier to follow. I have definitely had troubles understanding a number of other ones, so I don't know if it is me, or a shift in your writing style, but I am glad to be able to learn from this one.

@TED not sure if you have read my Quilt yet but I think you maybe very happy to see that Heat shock proteins have an entire levee dedicated to them. As you well know MMP9's are major heat shock proteins! Great comment and I promise I will expand upon that thought many times in the future. With regards to your comments on Mg Melatonin and Vitamin D…..remember that all our depeleted in cellular stess where cortisol is raised. The Mg is depeleted because it is a cofactor in many of the biochemical reactions that form stress hormones and in reactions that regulate inflammation and repair. Vitamin D is made from pregnenolone so in high stress times pregnenolone is shunted to cortisol production. This is called pregnenolone steal syndrome. This is why we are seeing pandemic low D levels. Melatonin is a major antioxidant of the CNS and it in cellular stress it is depleted and underconverted because sleep is disregulated. We need four hours of darkness to turn on melatonin and if we are not sleeping we never turn it on and it leads to insomnia and decreased autophagic repair during sleep. This allows the immune system to never catch up and allows continued inflammatory onslaught to occur and eventually lead to full blown autoimmune conditions. I am a much bigger fan of by passing melatonin by using oxytocin or progesterone. They are far more effective than melatonin in my experience.

"I am a much bigger fan of by passing melatonin by using oxytocin or progesterone. They are far more effective than melatonin in my experience."

First time heard of oxytocin, looked it up on wikipedia and it doesn't seem available OTC, same as progesterone where I live. In such a case, is there any other reason than effectiveness for not taking melatonin before going to bed as the alternative?

you can buy oxytocin over the counter in the states. The best way to get it is to have sex and complete it with orgasm. Orgasm stimulates a large release of oxytocin from the pituitary. Another way to do this is nipple massage for a few minutes.

How many mgs per orgasm? ..just joking. By searching this comment section again (it seems it's not made easy to find them on purpose in this blog..;-) also found the other article, 'What Casey and OJ have in common', where you don't seem to really be against melatonin supplementation either.

To Isis: Though being confused on these issues as well, from some reading here it seems to my Dr. Kruse would supplement DHEA according to repeated blood-test results.

..if I only wouldn't forget the titles. ..and had a doc who knew about the importance and implications of hormone testing. On my last consultation he asked what an aromatase inhibitor would be..

Meanwhile I titrated carefully from 10 to now 20mgs/day and try to be sensitive to side effects of overdoing. But rather sooner than later I'll have to pay for the test.

"..just joking-"

Actually not really funny if in the situation I was last year with no libido at all.. Any more details about 'nibble massage'? Guess it has to be gentle and best before falling asleep? Any indications that it works?

Trust me it works…….with persistence it will lead to better sleep and a rising DHEA and lowered IL-6 level. Most people dont check it. But if you starting DHEA is real low you will need brisk massage and a long time…..if you jump start it with say some DHEA and an orgasm here and there……..well then your cooking with gas.

WOW the things you learn. I used to do this when i was little. at bed time. it stopped working when i was 10 or so. That must have been when i ran out of the ability to self medicate from the abuse i suffered. It is also when my weight started coming on in great measure. 30 years later can i rebuild the stores?

Could you please give some guidelines for the non-biochemist? What supplements and dietary changes do you recommend for fighting MS. I'm taking D3. Do I need to take melatonin? Will that help? What else can and should I take? Thank you.

@Emily In my first paragraph I said this, The amount of methyl and acetyl groups come from our diets. For example, when we have low methylation in our diet, our DNA becomes hypomethylated. Lower levels of methylation correlates with development of higher rates of cancer and with autoimmune conditions"

I learned about epigenetics from Dr. Bruce Lipton's "Biology of Belief" and came away with an impression that other than eye color, hair, etc., our DNA is largely controlled by our thoughts. My wife, who has read mind/body books by the trainload advocates same.

I prolly missed some reference in Lipton's book somewhere, but I felt something was missing. How can a child "think" autonomic biochemical processes, let alone an adult. And the suggestion at the end of the book to go see a "psych-k" practitioner, meditation, etc., left me at a loss as to how on earth Fran's little sickly little son will EVER get a handle on what is going on with his poor health.

And after reading your blogs Jack, it has to be both spiritual and biochemical. In this reality, we live in both, it seems.

What is the main difference in biochemistry that the mind influences, and how does the natural genetic entity (our body) get out of balance? From the parents AND the environment, right?

Example:

Female born slack-jawed, narrow teeth, wispy hair, no eyebrows, sub-normal temps, moody, general malaise, autoimmune issues, aches and pains. Contracts double pneumonia while pregnant and nearly dies. Has male child who is much of the conditions as above. Her moodiness and character undoubtably further influence said son.

Said son blames himself for not being good enough, strong enough, smart enough, and seeks a way out through natural dietary means suggested by mother's lifelong search for relief.

@Martin I think I get your meaning here. I think mind body connection is a misnomer. Our mind is a product of biochemical and endocrine secretions. And we can alter our epigenetics by thoughts alone. We are the only animal that can do so.

When we alter our epigenetics with thoughts, a particular hormone release, say cortisol, alters our genes. But that's an easy one – fight or flight. The cortisol is the result of the "thought". How about the thyroid, estrogen, testosterone? It sounds like imbalances at birth and along the way can alter our gene expression as well. Fat gals having fat children, etc. If I remember my leptin reading, it gets set epigenetically. And resetting leptin is an epigenetic activity?

You are the Man. For decades I've been looking for you and the information you are so graciously sharing – an Optimal Life. Most guys have sports heroes, mine are science/art/craftsman types. You, in every sense of the word, a Hero to so many of us.

@Martin Thanks for the kind words. Im no hero…..Im doing my job to help people. All our thoughts modulate leptin status which in turn alters all the other hormones you mentioned which are also under its control. Everything is tied to together. Hence you see the "quilt concept" in my blog.

Some advocate the use of oils like evening primrose and black currant seed along with fish oil to help with inflammation in MS. Since these oils are high in omega 6s would you recommend not taking them? Thanks!

Dr. Kruse, I have a new client in my personal training business who has M.S. She is wheelchair confined. She has been eating lentils, peas, buckwheat, and arrowroot because of her "very rare" blood type "A positive A2" and "teacher" genome. A nutritionist told her to eat those foods, lots of raw veggies pureed, and fish. She is resisting my advice to stop eating lentils, peas, and buckwheat (due to damaging lectins) and eat a Paleo diet. Please, is there any significance to her blood type and genome in the face of M.S.? Isn't it top priority to omit all grains, lentils, peas, buckwheat, and of course dairy and nightshades (especially tomatoes)? She watched Terry Wahls and Prof. Cordain's videos.

@Sheryl……your friend is going to kill herself. She needs to adapt or be prepared for a miserable life. Dr Wahl's protocol is awesome and I fully endorse it…….but I take it further. She needs a ton of CO added and more K2 and D3 to get that gut in order. IV glutathione is also a huge help in AI as I outlined in the Leaky Gut Rx.

Dr. Kruse, I've reread and printed both this and your Leaky Gut Rx. I will go over them with her plus see to it I get her on Dr. Wahl's protocol. I will reinforce her need for Extra CO(she had a tiny jar), keep on her about getting her D3 up (it was dreadfully low at only 40 something), and look into her K2. Thank you, I greatly appreciate your thoughts!

Very interesting post, Dr Kruse. I have MS along with a number of other autoimmune diseases and I have taken compounded DHEA since 2002. I have also been Paleo-ish for about 7 years. The MS is progressing quite slowly but it's definitely progressing.

If you have the time, would you mind giving me your opinion on the hypothesis of the association of "Chronic cerebrospinal venous insufficiency" (CCSVI) and multiple sclerosis (MS). I am considering the recommended treatment of a shunt given that paleo et al and supplementation is not slowly nor reversing the condition.

@Claudia the shunt is not a good option in my view. i think most people with MS get hydrocephalus ex vaceo and they get sold a bill of goods on the shunt. I think the reason for this is because MS leads to neuronal loss because of the altered neuronal biogenesis. In my view you need to contact Terry Wahl's and get on her protocol……its pretty close to my own but she uses more vegetables than I do. I think those with MS need very aggressive treatments for the leaky gut. Most need IV glutathione but few get it. Terry cured herself with real food.

Thanks for all of the great advice Dr. Kruse, it's so nice of you to make yourself available to questions! To make a long story short, I was diagnosed with R&R MS in 2009, went on a CRAB drug for two years which made me sick three days every week – it never got better like my neuro said it would and he kept prescribing more drugs to counteract the side effects. At any rate I went off of the CRAB in September 2011 and have been on a strict (no dairy, no gluten, no legumes, I do eat meat though, I'm not a vegan) diet since then and have made considerable progress, I feel much better! The only problem is that while I was on the CRAB drug I lost a considerable amount of weight, well, considerable for me, I've always hovered around 125, I'm 5'6". Now I weight in at around 109, which is too thin, I'm 54 years old (female). However, since I am not eating dairy or gluten, I am having a hard time finding anything to eat that would pack on a few pounds – preferably muscle as while on the CRAB I never felt good enough to exercise either so I'm probably what you would call "skinny flabby." Do you have any suggestions on what I can do to beef up a little without going off my diet, which seems to be working well for me?

@Deb I answer in between patients or on bathroom breaks on my iphone! You need to adapt to fish, shell fish then grass fed meat!!!! Stay away from dairy and all grains……and you are skinny fat because your diet does not support your hormones……you control that choice with your choices. You might want to seriously consider lots of natural unprocessed Whey protein……The quality of our decisions forms the life we lead.

Wow, that was really quick with the reply, I must have caught you just at the right time! The hormones make a lot of sense because I eat like a pig, about twice as much as my husband, and never gain weight. O.K., if I can do without dairy and gluten (which was really hard initially), surely I can make myself eat fish! I will start today! I will also pay closer attention to make sure the beef I eat is grass fed and also check into the whey. Thanks so much, it is so great to run across a doctor who really cares about people and is anxious to share his knowledge!

@Deb it was after a deposition……so i was in a good mood. I got paid to piss off some lawyers. OK…….back to why I do this. I care about people and healthcare because people are dying slowly at the hands of conventional wisdom, or the standard of care as a barrister would say, and I hear people and doctors bitching about it daily. Instead of bitching I have decided to try to change healthcare and my profession……..the best way I know to do this is to first become the change I seek and then sprinkle it all over the things I say, do or touch. The best way to get organizational transformation is to change the manner in which they think. I am doing it to them and to you right now.

I am no longer them and you and them know it. They are still trying to figure out why and you just are happy that I am this nuts to do it for free.

Dr Kruse, Thank you for all this information. Keep up all that science-no dumming down please. Your blogs are great and the comments are very enlightening.Am following the leaky gut Rx, no gall bladder for 20yrs. Haven't read about anyone not liking the Coconut oil–and what clever tricks they have employed to keep it down? It makes me reach-can't stand it or the smell!!!but I try. Once I get optimal D3 levels, will I ever manage to raise my Hdl without sufficient co?

Hello Jack! I have a client with M.S. and have been working closely with her to omit all grains, legumes, and dairy, etc., plus she made an appointment with a naturopath for tests of allergies, hormones, and mineral, vitamin deficiencie, etc. I used your site to compile some things for her naturopath to test, thank you! But, her question is about peas. You see, she has a garden in which she planted peas and she is wondering if she can eat just the pea pods? Are pea pods safe, Jack?

Hello Jack. My MS client is searching for quick foods she can have on hand for when she is suddenly hungry. Is “brown rice protein” okay for her? It is found in a nutrition bar with all the other ingredients acceptable & has no dairy, gluten, soy, etc. Do you have any other suggestions for her? She doesn’t cook much.

As I suspected. It’s tough since she says she does not like meat,did not comfortable cooking, & was eating frozen meals, cookies, & lots of pasta when I met her. She has made drastic changes such as free of gluten, lentils, nightshades. Although, her husband still offers her crap like pizza. I need to get him on board, but is he willing? Looks like its time to invest in Dr. Wahl’s book… And continue reinforcing the need for grass fed meats, though she doesn’t like to talk about eating animals. Thank you Jack! BTW, I’m loving my cold tub w/ice, lost 14 lbs & feel amazing!

Good morning Jack. My MS client was feeling much better after a couple months on an autoimmune Paleo diet, exercise with me, & supplements suggested from your articles. She was gaining strength, energy, and a positive attitude. Although, she had a Botox treatment about 6 weeks ago in her legs &, since then, has been losing steam. She is back to work as a school teacher, part time, but uses her scooter much more and is more fatigued. I looked into the Botox and found itin locks acetylcholine, in turn inhibiting contractions. Please, what do you think about the Botox? Seems apparent it is causing her weakness. I guess we will wait for it to wear off? She doesn’t want to have her legs done again, but it seemed to help her hands in the past.

About Dr. Kruse

Dr. Jack Kruse is a respected neurosurgeon and CEO of Optimized Life, a health and wellness company dedicated to helping patients avoid the healthcare burdens we typically encounter as we age. He is a member of the American Association of Neurological Surgeons, the Congress of Neurologic Surgeons, and Age Management Medicine Group.